Lysosomal dysfunction is involved in apoptotic cell death in a Parkinsonism model

GOROJOD R.; ALAIMO, A; KOTLER M.L

Huerta Grande Cordoba

Congreso; XXVI Congreso Anual de la SAN; 2011

SAN

Lysosomal dysfunction has been widely related to neurodegeneration. Moreover, recent reports have linked abnormal protein accumulation in Parkinson¥s disease to ROS-mediated lysosomal permeabilization, degradation failures, proteases translocation to cytosol (e.g. Cathepsins B/D) and cleavage of ectopic targets and cell death. Manganism is a Parkinsonism induced by chronic manganese (Mn) overexposure. Considering that Manganism shares biochemical pathways with Parkinson?s disease and several studies point out astrocytes as the first target of Mn- induced damage, the aim of the this work was to study the possible link between lysosomal disruption and apoptotic cell death in rat astrocytoma C6 cells. Using LysoTracker staining we detected large structures resembling lysosomal inclusion bodies. Moreover, Cathepsin B inhibitor (Ca-074 Me, 1ìM), Cathepsin D inhibitor (Pepstatin A, 10ìM) and the V-ATPase inhibitor (Bafilomycin A1, 0.1nM) prevented cell death, caspases-8 and -3 activation and the FasL protein levels increment. These novel data suggest that lysosomal pathway is a potential target for therapeutic intervention in Mn-induced Parkinsonism and probably in other neurodegenerative conditions